The inner ear is the innermost part of the vertebrate ear where two sensory organs are hosted in the temporal bone:                The cochlea, dedicated to the auditory function, converting sound pressure patterns from the outer ear into electrochemical impulses which are passed on to the brain via the auditory nerve. The cochlea constitutes the ventral region of the inner ear and it contains the organ of Corti that comprises mechanosensory hair cells and supporting cells.        The vestibular system, dedicated to balance, acceleration, and gravity. This organ has a totally different function from cochlea, said function consisting in the detection of linear and angular accelerations of the head in order to transmit to the brain information on movements to achieve the equilibration function in collaboration with visual and proprioceptive information. It is also constituted of mechanosensory hair cells that convert mechanical actions into electrical potentials, and supporting cells.        
Although these two organs have sensory hair cells responsible of the receptor potential and the subsequent action potentials, their distinct morphology, synaptic connections and overall function imply differences in molecular and cellular mechanisms underlying their action.
The vestibular system and the cochlea exhibit organ-dependent differences. Indeed, numbers of ion channels and neurotransmitter-gated receptors are differently expressed in those sensory organs. This is particularly true for ions channels involved in nerve cells excitability. As such, endogenous heterogeneity is for example responsible for very strong differences in action potential discharge patterns between the cochlea and the vestibule (Zun-Li M O and Robin Davis, 1997. J Neurophysiol. 77(3):1294-305; Eatock et al., 2008 J. Exp Biol. 211(Pt 11):1764-74). Therefore, impairing/modulating the expression or function of ions channels or receptor, either pharmacologically or genetically can have significantly different consequences on hearing and balance functions. Similarly, when receptors or ion channels expressed in one organ have unknown mechanisms, their likely effectors or molecular partners in the other inner ear organ are hard to foretell, and hence the outcome of their modulation/mutation is unpredictable itself.
In a more specific example, Kv7. Potassium channels family associated with neurons excitability are expressed in both tissue neurons, their modulation or mutation have very distinct functional consequences on the two sensory modalities: a progressive and severe deafness (Kharkovets T. et al., 2006 EMBO J. 25(3):642-652) but normal balance function (Spitzmaul G et al., 2013 J Biol Chem. 288(13):9334-44).
In summary, such structural, functional and pathological differences between the cochlea and the vestibule lead the search for cochlear therapeutic treatment as being highly specific to this peculiar sensory organ.
Tinnitus is a phantom sensation of hearing in the absence of external sounds. It refers to objective tinnitus, which is caused by sound generated somewhere in the body and subjective tinnitus which is the perception of meaningless sounds without any physical sound being present. Tinnitus affects approximately 10% of the population. Approximately 50 million US adults reported having any tinnitus, and 16 million US adults reported having frequent tinnitus in the past year. The prevalence of frequent tinnitus increases with age, peaking at 14.3% between 60 and 69 years old. Tinnitus may significantly impair quality of life as it causes irritability, agitation, stress, insomnia, anxiety and depression. In fact, for one in 100 adults, tinnitus affects their ability to lead a normal day-to-day life.
Subjective tinnitus is the perception of sound without any auditory stimulus. Many people experience transient tinnitus lasting seconds or minutes after exposure to loud noise. The sounds associated with subjective tinnitus have been described as ringing, hissing, water running, humming, crickets, cicadas, whistling, wind blowing. Most patients experience a high pitch noise typically above 3,000 Hz. Although there is no consensus on a single and common pathomechanisms to tinnitus, there is currently cumulative evidence for a main peripheral auditory system theory of subjective tinnitus. Spontaneous otoacoustic emissions, increased spontaneous activity in the cochlear area such as aberrant firing of the auditory nerve and discordant dysfunction of damaged outer hair cells and intact inner hair cells have been postulated as putative cause for tinnitus.
Due to the lack of pathophysiological bases, the rationale behind pharmacological treatments for tinnitus is to treat the co-morbidities that come along with tinnitus, like depression and anxiety. Others treatments use drugs which are effective in disorders thought to share some commonalities with tinnitus, like anticonvulsants used in epilepsy and the calcium antagonist gabapentin used in neuropathic pain. Although a wide variety of compounds is used off-label to treat tinnitus patients, there is still no US Food and Drug Administration (FDA) or European Medicines Agency (EMA) approved drug on the market. The list of used compounds includes anticonvulsants, anxiolytic, antidepressants, NMDA antagonists, cholinergic antagonists, antihistamines, vasodilators, antipsychotics, and calcium antagonists. For example, WO2010113109 and WO2012/042314 described the use of cyclobenzaprine for treating tinnitus.
However, most drugs have not proven sufficient effectiveness in randomized controlled clinical trials in order to be approved and marketed specifically for tinnitus.
The present invention aims to provide a new method for treating tinnitus.